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Sökning: WFRF:(Lundgren Helena)

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1.
  • Chalkias, Helena, et al. (författare)
  • Barcelona 2009 – inte bara fotboll
  • 2009
  • Ingår i: Svensk gris med knorr. - 1650-5077. ; , s. 30, 32-
  • Tidskriftsartikel (populärvet., debatt m.m.)
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2.
  • Hawamdeh, Shurouq, 1982, et al. (författare)
  • Midwives’ attitude towards labour pain: Expectations and perceptions by Jordanian women
  • 2016
  • Ingår i: NJF congress, May 2016, Sweden..
  • Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
    • Background: In Jordan, as in other countries, the majority of women give birth in public hospitals where the midwives are the main birth attendants. Although most women have trust in their midwives; there are studies describing dissatisfaction of childbirth experience, fears associated with experiencing painful births and ineffective pain management during childbirth. Thus, there is a need to understand the Jordanian midwives' attitude towards labour pain from both the midwives and the women’s perspectives. Aim: To explore the Jordanian midwives' attitude towards labour pain by assessing the midwives' knowledge and attitude towards pain and the women's expectations and perceptions of their midwives' approach towards pain. Methods: The research took place in the largest public hospital in Jordan in the postnatal ward and involved midwives and their clients, including 60 midwives (out of 61 randomly sampled midwives), who responded to a study-specific validated survey for midwives (Survey Questionnaire for Midwives), and 360 women (out of 384 sampled women), who responded to a study-specific validated survey for women (Survey Questionnaire for Women). Findings: The study is ongoing. The findings are presented at the NJF conference (May 2016) and as a part of doctoral thesis that should be defended in May 2017.
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3.
  • Nilvér, Helena, et al. (författare)
  • Women's childbirth experiences in the Swedish Post-term Induction Study (SWEPIS) : a multicentre, randomised, controlled trial
  • 2021
  • Ingår i: BMJ Open. - : BMJ Publishing Group Ltd. - 2044-6055. ; 11:4
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVE: To compare childbirth experiences in women randomly assigned to either induction of labour at 41 weeks or to expectant management until 42 weeks, in the Swedish Post-term Induction Study.DESIGN: A register-based, multicentre, randomised, controlled, superiority trial.SETTING: Women were recruited at 14 hospitals in Sweden, 2016-2018.PARTICIPANTS: Women with an uncomplicated singleton pregnancy were recruited at 41 gestational weeks.INTERVENTIONS: The women were randomly assigned to induction of labour at 41 weeks (induction group, n=1381) or expectant management until 42 weeks (expectant management group, n=1379).OUTCOME MEASURES: As main outcome, women's childbirth experiences were measured using the Childbirth Experience Questionnaire version 2 (CEQ2), in 656 women, 3 months after the birth at three hospitals. As exploratory outcome, overall childbirth experience was measured in 1457 women using a Visual Analogue Scale (VAS 1-10) within 3 days after delivery at the remaining eleven hospitals.RESULTS: The total response rate was 77% (2113/2760). There were no significant differences in childbirth experience measured with CEQ2 between the groups (induction group, n=354; expectant management group, n=302) in the subscales: own capacity (2.8 vs 2.7, p=0.09), perceived safety (3.3 vs 3.2, p=0.06) and professional support (3.6 vs 3.5, p=0.38) or in the total CEQ2 score (3.3 vs 3.2, p=0.07), respectively. Women in the induction group scored higher in the subscale participation (3.6 vs 3.4, p=0.02), although with a small effect size (0.19). No significant difference was observed in overall childbirth experience according to VAS (8.0 (n=735) vs 8.1 (n=735), p=0.22). CONCLUSIONS: There were no differences in childbirth experience, according to CEQ2 or overall childbirth experience assessed with VAS, between women randomly assigned to induction of labour at 41 weeks or expectant management until 42 weeks. Overall, women rated their childbirth experiences high.TRIAL REGISTRATION NUMBER: ISRCTN26113652.
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4.
  • Ahlberg, Erik, et al. (författare)
  • "Vi klimatforskare stödjer Greta och skolungdomarna"
  • 2019
  • Ingår i: Dagens nyheter (DN debatt). - 1101-2447.
  • Tidskriftsartikel (populärvet., debatt m.m.)abstract
    • DN DEBATT 15/3. Sedan industrialiseringens början har vi använt omkring fyra femtedelar av den mängd fossilt kol som får förbrännas för att vi ska klara Parisavtalet. Vi har bara en femtedel kvar och det är bråttom att kraftigt reducera utsläppen. Det har Greta Thunberg och de strejkande ungdomarna förstått. Därför stödjer vi deras krav, skriver 270 klimatforskare.
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5.
  • Andersson Svärd, Agnes, et al. (författare)
  • Decreased HLA-DQ expression on peripheral blood cells in children with varying number of beta cell autoantibodies
  • 2020
  • Ingår i: Journal of Translational Autoimmunity. - : Elsevier BV. - 2589-9090. ; 3
  • Tidskriftsartikel (refereegranskat)abstract
    • The risk for type 1 diabetes is strongly associated with HLA-DQ and the appearance of beta cell autoantibodies against either insulin, glutamate decarboxylase (GAD65), insulinoma-associated protein-2 (IA-2), or zinc transporter 8 (ZnT8). Prolonged exposure to autoantibodies may be related to T cell exhaustion known to occur in chronic infections or autoimmune disorders. It was hypothesized that autoantibody exposure may affect HLA-DQ expression on peripheral blood cells and thereby contribute to T cell exhaustion thought to be associated with the pathogenesis of type 1 diabetes. The aim of this study was to determine whether autoantibody exposure as an expression of autoimmunity burden was related to peripheral blood cell HLA-DQ cell surface expression in either 1) a cross-sectional analysis or 2) cumulative as area under the trajectory of autoantibodies during long term follow-up in the Diabetes Prediction in Skåne (DiPiS) study. Children (n = 67), aged 10-15 years were analyzed for complete blood count, HLA-DQ cell surface median fluorescence intensity (MFI), autoantibody frequency, and HLA genotypes by Next Generation Sequencing. Decreased HLA-DQ cell surface MFI with an increasing number of autoantibodies was observed in CD16+, CD14+CD16-, CD4+ and CD8+ cells but not in CD19+ cells and neutrophils. HLA-DQ cell surface MFI was associated with HLA-DQ2/8 in CD4+ T cells, marginally in CD14+CD16- monocytes and CD8+ T cells. These associations appeared to be related to autoimmunity burden. The results suggest that HLA-DQ cell surface expression was related to HLA and autoimmunity burden.
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6.
  • Andersson Svärd, Agnes, et al. (författare)
  • Possible Relationship between the HLA-DRA1 Intron Haplotype of Three Single-Nucleotide Polymorphisms in Intron 1 of the HLA-DRA1 Gene and Autoantibodies in Children at Increased Genetic Risk for Autoimmune Type 1 Diabetes
  • 2022
  • Ingår i: ImmunoHorizons. - : The American Association of Immunologists. - 2573-7732. ; 6:8, s. 614-629
  • Tidskriftsartikel (refereegranskat)abstract
    • Recently, a haplotype of three single-nucleotide polymorphisms (tri-SNP) in intron 1 of the HLA-DRA1 gene was found to be strongly associated with type 1 diabetes risk in HLA-DR3/3 individuals. The tri-SNP reportedly function as “expression quantitative trait loci,” modulating HLA-DR and -DQ expression. The aim was to investigate HLA-DRA1 tri-SNPs in relation to extended HLA class II haplotypes and human peripheral blood cell HLA-DQ cell-surface median fluorescence intensity (MFI), the first-appearing islet autoantibody, and autoimmunity burden. A total of 67 healthy subjects (10–15 y) at increased HLA risk for type 1 diabetes and with (n = 54) or without (n = 13) islet autoantibodies were followed longitudinally in the Diabetes Prediction in Skåne study. Among four tri-SNPs, AGG (n = 67), GCA (n = 47), ACG (n = 11), and ACA (n = 9), HLA-DQ cell-surface MFI on CD4+ T cells was lower in AGG than GCA (p = 0.030) subjects. Cumulative autoimmunity burden was associated with reduced HLA-DQ cell-surface MFI in AGG compared with GCA in CD16+ cells (p = 0.0013), CD4+ T cells (p = 0.0018), and CD8+ T cells (p = 0.016). The results suggest that HLA-DRA1 tri-SNPs may be related to HLA-DQ cell-surface expression and autoimmunity burden.
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7.
  • Blom, Hans (författare)
  • Purification Processes for Complex Biomacromolecules
  • 2012
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • This thesis details various techniques and considerations for the purification of complex biomacromolecules. Initially an α-mannosidase from babaco fruit was purified using anion exchange-, lectin affinity- and size exclusion chromatography.  The enzyme was approximately 260-280 kDa in size with an apparent an unusual octagonal stoichiometry and displayed properties similar to other known plant α-mannosidases. Mucins were fractionated by ion exchange and size exclusion chromatography to assess the properties that govern the mucin surface coating interactions in biomaterial research.  Commercially available mucins, of bovine and porcine origin, as wells as crude human mucin were tested. All showed to consist of a population of molecules which differ in size, charge and composition. The third part of the thesis concerns different aspects of plasmid DNA purification processes.A two-step method for analysis of plasmid DNA consisting of size exclusion followed by thiophilic adsorption chromatography was evaluated. It allowed determination of the supercoiled plasmid DNA concentration in all process steps without requirement for extensive sample preparation. This method was shown to be fully comparable in terms of accuracy to capillary gel electrophoresis, considered as the industry standard.Purification of plasmid DNA generally involves bacterial cell alkaline lysis, which creates a solution with flocculate material which needs to be removed prior to further processing. The addition of ammonium hydrogen carbonate to the suspension was evaluated to clarify the solution. The released carbon dioxide and ammonium lifts the flocculate to the surface and allows draining of a clear solution. The method is fully scalable, does not affect the plasmid DNA quality and requires no special equipment.Thiophilic adsorption chromatography was evaluated for simplification of an existing commercial large scale purification process and was shown to increase both product purity and yields of several tested plasmids. Also, implementation of this step significantly reduced overall production process time.   
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8.
  • Brandhorst, Heide, 1962-, et al. (författare)
  • The importance of tryptic-like activity in purified enzyme blends for efficient islet isolation
  • 2009
  • Ingår i: Transplantation. - 0041-1337 .- 1534-6080. ; 87:3, s. 370-5
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: The isolation of islets from the human pancreas critically depends on an efficient enzyme blend. Previous studies have solely focused on the presence of collagenase and neutral protease/thermolysin. Despite improved characterization of these components, the lot-related variability in efficacy still persists suggesting that additional so far disregarded enzymes are required for efficient islet cleavage. METHODS: Varying activities of a tryptic-like enzyme were identified within collagenase NB1 lots, which were selected according to a matched ratio between tryptic-like and collagenase activity (TLA-ratio). Rat and human pancreata were processed with current standard procedures. RESULTS: Increasing the TLA-ratio from 1.3% to 10% reduced pancreas dissociation time in rats by 50% without affecting islet yield, viability, or posttransplant function in diabetic nude mice. Enhancing the TLA-ratio from 1.3% to 12.6% for human pancreas processing resulted in a significant reduction of recirculation time and increased incrementally human islet yield without affecting purity, in vitro function or recovery after culture. Optimized pancreas digestion correlated with a higher percentage of islet preparations fulfilling quality criteria for clinical transplantation. CONCLUSIONS: We conclude that TLA is an effective component that should be included in moderate amounts in enzyme blends for human islet isolation to optimize the efficiency and minimize the lot-related variability.
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10.
  • Bäck, Helena, et al. (författare)
  • Svenska lärosätens ansvar vid mäns våld mot kvinnor och våld i nära relationer
  • 2023
  • Rapport (övrigt vetenskapligt/konstnärligt)abstract
    • Kvinnor riskerar att utsättas för våld oavsett var de lever och den farligaste platsen där de grövsta våldsbrotten sker är i kvinnors egna hem. För dem som utsätts för våld kan därför arbetsplatsen uppfattas som en trygg och stödjande plats. Dock tyder tidigare forskning på att våldet fortsätter på eller i närheten av arbetsplatsen, det är därför viktigt att det finns riktlinjer och rutiner som adresserar sådant våld. Syftet med denna rapport var att kartlägga om svenska lärosäten har riktlinjer och rutiner om mäns våld mot kvinnor och våld i nära relationer. I kartläggningen fann vi att enbart ett av 28 lärosäten har någon form av riktlinje/rutin som adresserar mäns våld mot kvinnor och våld i nära relationer. Dock saknar alla lärosäten riktlinjer och rutiner som vänder sig till studenter. När sådana saknas finns en risk att de som utsatts för våld inte uppmärksammats, vilket kan leda till individuella fysiska, psykiska och sociala konsekvenser, samt att arbetslivet påverkas negativt. I rapporten redovisar vi hur situationen ser ut vid Mittuniversitet, samt redogör för det förändringsarbete som vi initierat vid lärosätet. Vi hoppas att den här rapporten kan fungera som inspiration, inte bara gällande framtagande av riktlinjer och rutiner, utan också för framtida forskning, så att mäns våld kan upphöra och att de som utsätts för våld uppmärksammas och kan få adekvat hjälp och stöd.
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11.
  • Bäck, Helena, et al. (författare)
  • Universitetens ansvar när män utsätter kvinnor för våld
  • 2023
  • Konferensbidrag (refereegranskat)abstract
    • Mäns våld mot kvinnor är det största hotet mot jämställdhet. Våld mot kvinnor förekommer överallt i samhället – kvinnor som är anställda eller studerar på universitetet är inget undantag. Samtidigt saknar många universitetsanställda kunskaper om hur de ska möta en kollega eller student som berättar att en man i hennes närhet utsätter henne för våld. Mittuniversitetet har inte heller någon handlingsplan för hur man som arbetsgivare eller utbildningsanordnare hanterar uppgifter och agerar när en anställd eller student utsätts för våld. I vår presentation kommer vi att visa att de allra flesta lärosäten i Sverige saknar riktlinjer/policy i frågor kring mäns våld mot kvinnor och våld i nära relationer. Vi menar att Mittuniversitet som myndighet har ett ansvar att som arbetsgivare agera i en stor och viktig samhällsfråga, och kommer också att presentera en rad möjliga åtgärder som universitetet skulle kunna vidta. Mittuniversitetet skulle därmed ligga i framkant bland lärosätena genom att ta fram riktlinjer och policys, samt utbilda chefer och medarbetare om mäns våld mot kvinnor. Frågor om våld i nära relationer bör också finnas med i medarbetarsamtalets material samt i kravspecifikationer för framtida upphandling av företagshälsovård.
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13.
  • Cirenajwis, Helena, et al. (författare)
  • Molecular stratification of metastatic melanoma using gene expression profiling: prediction of survival outcome and benefit from molecular targeted therapy.
  • 2015
  • Ingår i: Oncotarget. - : Impact Journals, LLC. - 1949-2553. ; 6:14, s. 12297-12309
  • Tidskriftsartikel (refereegranskat)abstract
    • Melanoma is currently divided on a genetic level according to mutational status. However, this classification does not optimally predict prognosis. In prior studies, we have defined gene expression phenotypes (high-immune, pigmentation, proliferative and normal-like), which are predictive of survival outcome as well as informative of biology. Herein, we employed a population-based metastatic melanoma cohort and external cohorts to determine the prognostic and predictive significance of the gene expression phenotypes. We performed expression profiling on 214 cutaneous melanoma tumors and found an increased risk of developing distant metastases in the pigmentation (HR, 1.9; 95% CI, 1.05-3.28; P=0.03) and proliferative (HR, 2.8; 95% CI, 1.43-5.57; P=0.003) groups as compared to the high-immune response group. Further genetic characterization of melanomas using targeted deep-sequencing revealed similar mutational patterns across these phenotypes. We also used publicly available expression profiling data from melanoma patients treated with targeted or vaccine therapy in order to determine if our signatures predicted therapeutic response. In patients receiving targeted therapy, melanomas resistant to targeted therapy were enriched in the MITF-low proliferative subtype as compared to pre-treatment biopsies (P=0.02). In summary, the melanoma gene expression phenotypes are highly predictive of survival outcome and can further help to discriminate patients responding to targeted therapy.
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14.
  • Eckeskog, Helena, et al. (författare)
  • Förståelsestrategiers möjlighet att utveckla kritisk literacy-kompetens
  • 2015
  • Ingår i: Critical literacy i svensk klassrumskontext. - Umeå : Umeå universitet. - 9789176012024 ; , s. 37-50
  • Bokkapitel (refereegranskat)abstract
    • Det övergripande syftet med artikeln är att reflektera över hur undervisning om förståelsestrategier är relaterade till kritisk literacy. Det mer specifika syftet är att analysera vilka förståelsestrategier som verkar ge eleverna access till ett innehåll. Med access avses i denna artikel hur eleverna tolkar, får tillgång till och kritiskt förstår ett innehåll. Skolverket (2012) konstaterar att svenska elever i lägre utsträckning får arbeta med förståelsestrategier jämfört med elever i andra deltagande länder i PIRLS 2011. Den teoretiska utgångspunkten för denna artikel är literacy-utveckling ur ett sociokulturellt perspektiv (Barton 2007) samt ett kritiskt literacy-perspektiv på förståelsestrategier utgår från Freire (1996) och Janks (2010). Studiens resultat visar att elever får access till ett innehåll när läraren använder förståelsestrategierna som en del av ett genuint samtal om texterna, när miljön i klassrummet är tillåtande, eleverna uppmuntras att ställa frågor och att elevernas frågor blir uppmärksammade. Det verkar även som om lärarens bemötande, exempelvis att lyssna in och fånga upp, spelar stor roll för elevernas förståelse samt hur och i vilken utsträckning eleverna tillåts att fråga och fundera omkring det de läst samt hur deras frågor och kommentarer bemöts och utvecklas av läraren.
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15.
  • Edqvist, Malin, 1971, et al. (författare)
  • Midwives’ lived experience of a birth where the woman suffers an obstetric anal sphincter injury - a phenomenological study
  • 2014
  • Ingår i: BMC Pregnancy and Childbirth. - : Springer Science and Business Media LLC. - 1471-2393. ; 14:258
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: The occurrence of obstetric anal sphincter injuries (OASIS) has increased in most high-income countries during the past twenty years. The consequences of these injuries can be devastating for women and have an impact on their daily life and quality of health. The aim of this study was to obtain a deeper understanding of midwives’ lived experiences of attending a birth in which the woman gets an obstetric anal sphincter injury. Methods: A qualitative study using phenomenological lifeworld research design. The data were collected through in-depth interviews with 13 midwives. Results: The essential meaning of the phenomenon was expressed as a deadlock difficult to resolve between a perceived truth among midwives that a skilled midwife can prevent severe perineal trauma and at the same time a coexisting more complex belief. The more complex belief is that sphincter injuries cannot always be avoided. The midwives tried to cope with their feelings of guilt and wanted to find reasons why the injury occurred. A fear of being exposed and judged by others as severely as they judged themselves hindered the midwives from sharing their experience. Ultimately the midwives accepted that the injury had occurred and moved on without any definite answers. Conclusions: Being caught between an accepted truth and a more complex belief evoked various emotions among the midwives. Feelings of guilt, shame and the midwife’s own suspicion that she is not being professionally competent were not always easy to share. This study shows the importance of creating a safe working environment in which midwives can reflect on and share their experiences to continue to develop professionally. Further research is needed to implement and evaluate the effect of reflective practices in relation to midwifery care and whether this could benefit women in childbirth.
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16.
  • Edqvist, Malin, 1971, et al. (författare)
  • Midwives' Management during the Second Stage of Labor in Relation to Second-Degree Tears-An Experimental Study
  • 2017
  • Ingår i: Birth. - : Wiley. - 0730-7659 .- 1523-536X. ; 44:1, s. 86-94
  • Tidskriftsartikel (refereegranskat)abstract
    • INTRODUCTION: Most women who give birth for the first time experience some form of perineal trauma. Second-degree tears contribute to long-term consequences for women and are a risk factor for occult anal sphincter injuries. The objective of this study was to evaluate a multifaceted midwifery intervention designed to reduce second-degree tears among primiparous women.METHODS: An experimental cohort study where a multifaceted intervention consisting of 1) spontaneous pushing, 2) all birth positions with flexibility in the sacro-iliac joints, and 3) a two-step head-to-body delivery was compared with standard care. Crude and Adjusted OR (95% CI) were calculated between the intervention and the standard care group, for the various explanatory variables.RESULTS: A total of 597 primiparous women participated in the study, 296 in the intervention group and 301 in the standard care group. The prevalence of second-degree tears was lower in the intervention group: [Adj. OR 0.53 (95% CI 0.33-0.84)]. A low prevalence of episiotomy was found in both groups (1.7 and 3.0%). The prevalence of epidural analgesia was 61.1 percent. Despite the high use of epidural analgesia, the midwives in the intervention group managed to use the intervention.CONCLUSION: It is possible to reduce second-degree tears among primiparous women with the use of a multifaceted midwifery intervention without increasing the prevalence of episiotomy. Furthermore, the intervention is possible to employ in larger maternity wards with midwives caring for women with both low- and high-risk pregnancies.
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19.
  • Elding Larsson, Helena, et al. (författare)
  • Safety and efficacy of autoantigen-specific therapy with 2 doses of alum-formulated glutamate decarboxylase in children with multiple islet autoantibodies and risk for type 1 diabetes : A randomized clinical trial
  • 2018
  • Ingår i: Pediatric Diabetes. - : Hindawi Limited. - 1399-543X .- 1399-5448. ; 19:3, s. 410-419
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVE: Treatments have failed to delay or stop the autoimmune process, preceding onset of type 1 diabetes. We investigated if autoantigen-specific treatment with alum-formulated glutamate decarboxylase (GAD-Alum) was safe and affected progression to type 1 diabetes in children with islet autoimmunity.METHODS: In an investigator-initiated, double-blind, placebo-controlled clinical trial, non-diabetic children aged 4 to 17.9 years with autoantibodies to glutamate decarboxylase (GADA) and at least one of insulinoma-associated protein 2, insulin or zinc-transporter 8, were randomized, stratified by 2 or ≥3 islet autoantibodies, to 2 injections of 20 μg GAD-Alum or placebo, 30 days apart. Main outcome was safety, investigated by adverse events, hematology, chemistry, thyroid and celiac autoimmunity and titers of islet autoantibodies, and efficacy, investigated by cumulative incidence of diabetes onset over 5-year follow-up. Secondary variables: change in first-phase insulin release (FPIR) after intravenous glucose tolerance tests, fasting, 120 minutes and Area under the curve (AUC) C-peptide and p-glucose after oral glucose tolerance tests and HbA1c.RESULTS: Fifty children (median age: 5.2) were assigned 1:1 to GAD-Alum or placebo, all receiving full treatment and included in the analyses. GAD-Alum did not affect any safety parameter, while GADA titers increased (P = .001). Time to clinical diagnosis was not affected by treatment (hazard ratio, HR = 0.77, P = .574) in the full population or in the separate stratum groups. Treatment did not affect any of the secondary variables.CONCLUSIONS: GAD-Alum as a subcutaneous prime and boost injection was safe in prediabetic young children but did not affect progression to type 1 diabetes. The safety of GAD-Alum should prove useful in future prevention studies.
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20.
  • Ghalwash, Mohamed, et al. (författare)
  • Islet autoantibody screening in at-risk adolescents to predict type 1 diabetes until young adulthood : a prospective cohort study
  • 2023
  • Ingår i: The Lancet Child and Adolescent Health. - 2352-4642. ; 7:4, s. 261-268
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Screening for islet autoantibodies in children and adolescents identifies individuals who will later develop type 1 diabetes, allowing patient and family education to prevent diabetic ketoacidosis at onset and to enable consideration of preventive therapies. We aimed to assess whether islet autoantibody screening is effective for predicting type 1 diabetes in adolescents aged 10−18 years with an increased risk of developing type 1 diabetes. Methods: Data were harmonised from prospective studies from Finland (the Diabetes Prediction and Prevention study), Germany (the BABYDIAB study), and the USA (Diabetes Autoimmunity Study in the Young and the Diabetes Evaluation in Washington study). Autoantibodies against insulin, glutamic acid decarboxylase, and insulinoma-associated protein 2 were measured at each follow-up visit. Children who were lost to follow-up or diagnosed with type 1 diabetes before 10 years of age were excluded. Inverse probability censoring weighting was used to include data from remaining participants. Sensitivity and the positive predictive value of these autoantibodies, tested at one or two ages, to predict type 1 diabetes by the age of 18 years were the main outcomes. Findings: Of 20 303 children with an increased type 1 diabetes risk, 8682 were included for the analysis with inverse probability censoring weighting. 1890 were followed up to 18 years of age or developed type 1 diabetes between the ages of 10 years and 18 years, and their median follow-up was 18·3 years (IQR 14·5–20·3). 442 (23·4%) of 1890 adolescents were positive for at least one islet autoantibody, and 262 (13·9%) developed type 1 diabetes. Time from seroconversion to diabetes diagnosis increased by 0·64 years (95% CI 0·34–0·95) for each 1-year increment of diagnosis age (Pearson's correlation coefficient 0·88, 95% CI 0·50–0·97, p=0·0020). The median interval between the last prediagnostic sample and diagnosis was 0·3 years (IQR 0·1–1·3) in the 227 participants who were autoantibody positive and 6·8 years (1·6–9·9) for the 35 who were autoantibody negative. Single screening at the age of 10 years was 90% (95% CI 86–95) sensitive, with a positive predictive value of 66% (60–72) for clinical diabetes. Screening at two ages (10 years and 14 years) increased sensitivity to 93% (95% CI 89–97) but lowered the positive predictive value to 55% (49–60). Interpretation: Screening of adolescents at risk for type 1 diabetes only once at 10 years of age for islet autoantibodies was highly effective to detect type 1 diabetes by the age of 18 years, which in turn could enable prevention of diabetic ketoacidosis and participation in secondary prevention trials. Funding: JDRF International.
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21.
  • Hagforsen, Eva, et al. (författare)
  • Women with palmoplantar pustulosis have disturbed calcium homeostasis and a high prevalence of diabetes mellitus and psychiatric disorders : a case-control study
  • 2005
  • Ingår i: Acta Dermato-Venereologica. - : Medical Journals Sweden AB. - 0001-5555 .- 1651-2057. ; 85:3, s. 225-232
  • Tidskriftsartikel (refereegranskat)abstract
    • Palmoplantar pustulosis is characterized by pustule formation in the acrosyringium. Nearly 50% of palmoplantar pustulosis sera produce immunofluorescence of the palmar papillary endothelium from healthy subjects, but also of the endothelium of normal parathyroid gland. With a case-control design the levels of calcium and parathyroid hormone in serum were measured in 60 women with palmoplantar pustulosis and 154 randomly selected population-based control women. One-third of the controls had been smokers, whereas 95% of the cases were or had been smokers. Mean age-adjusted serum calcium was increased in the patients compared with the controls (2.43 vs 2.36 mmol/l; p<0.0001), whereas the parathyroid hormone concentration was suppressed (23.2 vs 31.1 ng/l; p<0.0001). The plasma levels of parathyroid hormone-related protein were normal in patients but there was a strong expression of this protein in the acrosyringium both in palmoplantar pustulosis and control skin. As even a marginal elevation of serum calcium is associated with an increased risk for diabetes, cardiovascular disease and psychiatric disease, we analysed the risk for these disorders in palmoplantar pustulosis patients compared with that in the control group. Both diabetes mellitus and psychiatric disorders were associated with palmoplantar pustulosis with an odds ratio of 8.7 (95% CI 3.3-22.8) and 5.6 (95% CI 2.2-14.4), respectively. Palmoplantar pustulosis is a complex disease with an increased risk for several non-dermatological disorders. The role of the mildly increased serum calcium for the high risk for diabetes and depression deserves to be studied.
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23.
  • Harbst, Katja, et al. (författare)
  • Molecular and genetic diversity in the metastatic process of melanoma.
  • 2014
  • Ingår i: Journal of Pathology. - : Wiley. - 0022-3417 .- 1096-9896. ; 233:1, s. 39-50
  • Tidskriftsartikel (refereegranskat)abstract
    • Diversity between metastatic melanoma tumours in individual patients is known; however, the molecular and genetic differences remain unclear. To examine the molecular and genetic differences between metastatic tumours, we performed gene-expression profiling of 63 melanoma tumours obtained from 28 patients (two or three tumours/patient), followed by analysis of their mutational landscape, using targeted deep sequencing of 1697 cancer genes and DNA copy number analysis. Gene-expression signatures revealed discordant phenotypes between tumour lesions within a patient in 50% of the cases. In 18 of 22 patients (where matched normal tissue was available), we found that the multiple lesions within a patient were genetically divergent, with one or more melanoma tumours harbouring 'private' somatic mutations. In one case, the distant subcutaneous metastasis of one patient occurring 3 months after an earlier regional lymph node metastasis had acquired 37 new coding sequence mutations, including mutations in PTEN and CDH1. However, BRAF and NRAS mutations, when present in the first metastasis, were always preserved in subsequent metastases. The patterns of nucleotide substitutions found in this study indicate an influence of UV radiation but possibly also DNA alkylating agents. Our results clearly demonstrate that metastatic melanoma is a molecularly highly heterogeneous disease that continues to progress throughout its clinical course. The private aberrations observed on a background of shared aberrations within a patient provide evidence of continued evolution of individual tumours following divergence from a common parental clone, and might have implications for personalized medicine strategies in melanoma treatment. Published by John Wiley & Sons, Ltd. www.pathsoc.org.uk.
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24.
  • Hellström, Ann, 1959, et al. (författare)
  • Association of Docosahexaenoic Acid and Arachidonic Acid Serum Levels With Retinopathy of Prematurity in Preterm Infants
  • 2021
  • Ingår i: Jama Network Open. - : American Medical Association (AMA). - 2574-3805. ; 4:10
  • Tidskriftsartikel (refereegranskat)abstract
    • IMPORTANCE Supplementing preterm infants with long-chain polyunsaturated fatty acids (LC-PUFA) has been inconsistent in reducing the severity and incidence of retinopathy of prematurity (ROP). Furthermore, few studies have measured the long-term serum lipid levels after supplementation. OBJECTIVE To assess whether ROP severity is associated with serum levels of LC-PUFA, especially docosahexaenoic acid (DHA) and arachidonic acid (AA), during the first 28 postnatal days. DESIGN, SETTING, AND PARTICIPANTS This cohort study analyzed the Mega Donna Mega study, a randomized clinical trial that provided enteral fatty acid supplementation at 3 neonatal intensive care units in Sweden. Infants included in this cohort study were born at a gestational age of less than 28 weeks between December 20, 2016, and August 6, 2019. MAIN OUTCOMES AND MEASURES Severity of ROP was classified as no ROP, mild or moderate ROP (stage 1-2), or severe ROP (stage 3 and type 1). Serum phospholipid fatty acids were measured through gas chromatography-mass spectrometry. Ordinal logistic regression, with a description of unadjusted odds ratio (OR) as well as gestational age- and birth weight-adjusted ORs and 95% CIs, was used. Areas under the curve were used to calculate mean daily levels of fatty acids during postnatal days 1 to 28. Blood samples were obtained at the postnatal ages of 1, 3, 7, 14, and 28 days. RESULTS A total of 175 infants were included in analysis. Of these infants, 99 were boys (56.6%); the median (IQR) gestational age was 25 weeks 5 days (24 weeks 3 days to 26 weeks 6 days), and the median (IQR) birth weight was 785 (650-945) grams. A higher DHA proportion was seen in infants with no ROP compared with those with mild or moderate ROP or severe ROP (OR per 0.5-molar percentage increase, 0.49 [95% CI, 0.36-0.68]; gestational age- and birth weight-adjusted OR, 0.66 [95% CI, 0.46-0.93]). The corresponding adjusted OR for AA levels per 1-molar percentage increase was 0.83 (95% CI, 0.66-1.05). The association between DHA levels and ROP severity appeared only in infants with sufficient AA levels, suggesting that a mean daily minimum level of 7.8 to 8.3 molar percentage of AA was necessary for a detectable association between DHA level and less severe ROP. CONCLUSIONS AND RELEVANCE This cohort study found that higher mean daily serum levels of DHA during the first 28 postnatal days were associated with less severe ROP even after adjustment for known risk factors, but only in infants with sufficiently high AA levels. Further studies are needed to identify LC-PUFA supplementation strategies that may prevent ROP and other morbidities.
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25.
  • Hendriks, A. Emile J., et al. (författare)
  • Clinical care advice for monitoring of islet autoantibody positive individuals with presymptomatic type 1 diabetes
  • 2024
  • Ingår i: Diabetes/Metabolism Research and Reviews. - 1520-7552. ; 40:2
  • Tidskriftsartikel (refereegranskat)abstract
    • Background/Aim: Type 1 diabetes is an autoimmune disease that involves the development of autoantibodies against pancreatic islet beta-cell antigens, preceding clinical diagnosis by a period of preclinical disease activity. As screening activity to identify autoantibody-positive individuals increases, a rise in presymptomatic type 1 diabetes individuals seeking medical attention is expected. Current guidance on how to monitor these individuals in a safe but minimally invasive way is limited. This article aims to provide clinical guidance for monitoring individuals with presymptomatic type 1 diabetes to reduce the risk of diabetic ketoacidosis (DKA) at diagnosis. Methods: Expert consensus was obtained from members of the Fr1da, GPPAD, and INNODIA consortia, three European diabetes research groups. The guidance covers both specialist and primary care follow-up strategies. Results: The guidance outlines recommended monitoring approaches based on age, disease stage and clinical setting. Individuals with presymptomatic type 1 diabetes are best followed up in specialist care. For stage 1, biannual assessments of random plasma glucose and HbA1c are suggested for children, while annual assessments are recommended for adolescents and adults. For stage 2, 3-monthly clinic visits with additional home monitoring are advised. The value of repeat OGTT in stage 1 and the use of continuous glucose monitoring in stage 2 are discussed. Primary care is encouraged to monitor individuals who decline specialist care, following the guidance presented. Conclusions: As type 1 diabetes screening programs become more prevalent, effective monitoring strategies are essential to mitigate the risk of complications such as DKA. This guidance serves as a valuable resource for clinicians, providing practical recommendations tailored to an individual's age and disease stage, both within specialist and primary care settings.
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26.
  • Houben, Janne, et al. (författare)
  • The emotional well-being of parents with children at genetic risk for type 1 diabetes before and during participation in the POInT-study
  • 2022
  • Ingår i: Pediatric Diabetes. - : Hindawi Limited. - 1399-543X .- 1399-5448. ; 23:8, s. 1707-1716
  • Tidskriftsartikel (refereegranskat)abstract
    • Introduction: This study examined the emotional impact that parents experience when confronted with an increased genetic risk of type 1 diabetes (T1D) in their child. Population-based screening of neonates for genetic risk of chronic disease carries the risk of increased emotional burden for parents. Methods: Information was collected using a well-being questionnaire for parents of infants identified as having an increased risk for T1D in a multinational research study. Parents were asked to complete this questionnaire after they were told their child had an increased risk for T1D (Freder1k-study) and at several time points during an intervention study (POInT-study), where oral insulin was administered daily. Results: Data were collected from 2595 parents of 1371 children across five countries. Panic-related anxiety symptoms were reported by only 4.9% after hearing about their child having an increased risk. Symptoms of depression were limited to 19.4% of the parents at the result-communication visit and declined over time during the intervention study. When thinking about their child's risk for developing T1D (disease-specific anxiety), 47.2% worried, felt nervous and tense. Mothers and parents with a first-degree relative (FDR) with T1D reported more symptoms of depression and disease-specific anxiety (p < 0.001) than fathers and parents without a FDR. Conclusion: Overall, symptoms of depression and panic-related anxiety are comparable with the German population. When asked about their child's risk for T1D during the intervention study, some parents reported disease-specific anxiety, which should be kept in mind when considering population-based screening. As certain subgroups are more prone, it will be important to continue psychological screening and, when necessary, to provide support by an experienced, multidisciplinary team.
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27.
  • Hummel, Sandra, et al. (författare)
  • Early-childhood body mass index and its association with the COVID-19 pandemic, containment measures and islet autoimmunity in children with increased risk for type 1 diabetes
  • Ingår i: Diabetologia. - 0012-186X.
  • Tidskriftsartikel (refereegranskat)abstract
    • Aims/hypothesis: The aim of this study was to determine whether BMI in early childhood was affected by the COVID-19 pandemic and containment measures, and whether it was associated with the risk for islet autoimmunity. Methods: Between February 2018 and May 2023, data on BMI and islet autoimmunity were collected from 1050 children enrolled in the Primary Oral Insulin Trial, aged from 4.0 months to 5.5 years of age. The start of the COVID-19 pandemic was defined as 18 March 2020, and a stringency index was used to assess the stringency of containment measures. Islet autoimmunity was defined as either the development of persistent confirmed multiple islet autoantibodies, or the development of one or more islet autoantibodies and type 1 diabetes. Multivariate linear mixed-effect, linear and logistic regression methods were applied to assess the effect of the COVID-19 pandemic and the stringency index on early-childhood BMI measurements (BMI as a time-varying variable, BMI at 9 months of age and overweight risk at 9 months of age), and Cox proportional hazard models were used to assess the effect of BMI measurements on islet autoimmunity risk. Results: The COVID-19 pandemic was associated with increased time-varying BMI (β = 0.39; 95% CI 0.30, 0.47) and overweight risk at 9 months (β = 0.44; 95% CI 0.03, 0.84). During the COVID-19 pandemic, a higher stringency index was positively associated with time-varying BMI (β = 0.02; 95% CI 0.00, 0.04 per 10 units increase), BMI at 9 months (β = 0.13; 95% CI 0.01, 0.25) and overweight risk at 9 months (β = 0.23; 95% CI 0.03, 0.43). A higher age-corrected BMI and overweight risk at 9 months were associated with increased risk for developing islet autoimmunity up to 5.5 years of age (HR 1.16; 95% CI 1.01, 1.32 and HR 1.68, 95% CI 1.00, 2.82, respectively). Conclusions/interpretation: Early-childhood BMI increased during the COVID-19 pandemic, and was influenced by the level of restrictions during the pandemic. Controlling for the COVID-19 pandemic, elevated BMI during early childhood was associated with increased risk for childhood islet autoimmunity in children with genetic susceptibility to type 1 diabetes. Graphical Abstract: [Figure not available: see fulltext.]
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28.
  • Jacobs, An, et al. (författare)
  • Vitamin D insufficiency in infants with increased risk of developing type 1 diabetes : A secondary analysis of the POInT Study
  • 2024
  • Ingår i: BMJ Paediatrics Open. - 2399-9772. ; 8:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Background Vitamin D insufficiency (VDI) may be a factor in the development of type 1 diabetes (T1D). The aim of this study is to investigate the presence and persistence of VDI in a large cohort of infants with increased risk of developing T1D, in light of the differences in local supplementation guidelines. Methods In the POInT Study, a multicentre primary prevention study between February 2018 and March 2021 in Germany, Poland, Belgium, England and Sweden, including infants aged 4-7 months at high genetic risk of developing β-cell autoantibodies, vitamin D levels were analysed at each study visit from inclusion (4-7 months) until 3 years, with an interval of 2 months (first three visits) or 4-6 months (visits 4-8). The protocol actively promotes vitamin D sufficiency to optimise immune tolerance. VDI was defined as a concentration below 30 ng/mL and was treated according to local guidelines of participating centres. Recovery from VDI was defined as a concentration above or equal to 30 ng/mL on the subsequent visit after VDI. Results 1050 infants were included, of which 5937 vitamin D levels were available for analyses. VDI was observed in 1464 (24.7%) visits and 507 (46.1%) of these were not resolved at the next visit. The risk of having VDI was independently associated with season (higher in winter), weight (higher with increased weight), age (higher with increased age) and country (higher in England). The risk of not recovering from VDI was independently associated with the season of the previously determined VDI, which was higher if VDI was identified in winter. Conclusions VDI is frequent in infants with increased risk of developing T1D. Treatment guidelines for VDI do not seem effective. Increasing supplementation dosages in this patient population seems warranted, especially during winter, and increasing dosages more aggressively after VDI should be considered.
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29.
  • Jacobsen, Laura M., et al. (författare)
  • Heterogeneity of DKA Incidence and Age-Specific Clinical Characteristics in Children Diagnosed With Type 1 Diabetes in the TEDDY Study
  • 2022
  • Ingår i: Diabetes Care. - : American Diabetes Association. - 0149-5992. ; 45:3, s. 624-633
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVE The Environmental Determinants of Diabetes in the Young (TEDDY) study is uniquely capable of investigating age-specific differences associated with type 1 diabetes. Because age is a primary driver of heterogeneity in type 1 diabetes, we sought to characterize by age metabolic derangements prior to diagnosis and clinical features associated with diabetic ketoacidosis (DKA). RESEARCH DESIGN AND METHODS The 379 TEDDY children who developed type 1 diabetes were grouped by age at onset (0–4, 5–9, and 10–14 years; n = 142, 151, and 86, respectively) with com-parisons of autoantibody profiles, HLAs, family history of diabetes, presence of DKA, symptomatology at onset, and adherence to TEDDY protocol. Time-varying analysis compared those with oral glucose tolerance test data with TEDDY children who did not progress to diabetes. RESULTS Increasing fasting glucose (hazard ratio [HR] 1.09 [95% CI 1.04–1.14]; P = 0.0003), stimulated glucose (HR 1.50 [1.42–1.59]; P < 0.0001), fasting insulin (HR 0.89 [0.83–0.95]; P = 0.0009), and glucose-to-insulin ratio (HR 1.29 [1.16–1.43]; P < 0.0001) were associated with risk of progression to type 1 diabetes. Younger children had fewer autoantibodies with more symptoms at diagnosis. Twenty-three children (6.1%) had DKA at onset, only 1 (0.97%) of 103 with and 22 (8.0%) of 276 children without a first-degree relative (FDR) with type 1 diabetes (P = 0.008). Children with DKA were more likely to be nonadherent to study protocol (P = 0.047), with longer duration between their last TEDDY evaluation and diagnosis (median 10.2 vs. 2.0 months without DKA; P < 0.001). CONCLUSIONS DKA at onset in TEDDY is uncommon, especially for FDRs. For those without familial risk, metabolic monitoring continues to provide a primary benefit of reduced DKA but requires regular follow-up. Clinical and laboratory features vary by age at onset, adding to the heterogeneity of type 1 diabetes.
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30.
  • Jensen, Emil, et al. (författare)
  • Changes in temperature in preheated crystalloids at ambient temperatures relevant to a prehospital setting: an experimental simulation study with the application of prehospital treatment of trauma patients suffering from accidental hypothermia
  • 2024
  • Ingår i: BMC Emergency Medicine. - : BioMed Central (BMC). - 1471-227X. ; 24
  • Tidskriftsartikel (refereegranskat)abstract
    • BackgroundAccidental hypothermia is common in all trauma patients and contributes to the lethal diamond, increasing both morbidity and mortality. In hypotensive shock, fluid resuscitation is recommended using fluids with a temperature of 37–42°, as fluid temperature can decrease the patient’s body temperature. In Sweden, virtually all prehospital services use preheated fluids. The aim of the present study was to investigate how the temperature of preheated infusion fluids is affected by the ambient temperatures and flow rates relevant for prehospital emergency care.MethodsIn this experimental simulation study, temperature changes in crystalloids preheated to 39 °C were evaluated. The fluid temperature changes were measured both in the infusion bag and at the patient end of the infusion system. Measurements were conducted in conditions relevant to prehospital emergency care, with ambient temperatures varying between − 4 and 28 °C and flow rates of 1000 ml/h and 6000 ml/h, through an uninsulated infusion set at a length of 175 cm.ResultsThe flow rate and ambient temperature affected the temperature in the infusion fluid both in the infusion bag and at the patient end of the system. A lower ambient temperature and lower flow rate were both associated with a greater temperature loss in the infusion fluid.ConclusionThis study shows that both a high infusion rate and a high ambient temperature are needed if an infusion fluid preheated to 39 °C is to remain above 37 °C when it reaches the patient using a 175-cm-long uninsulated infusion set. It is apparent that the lower the ambient temperature, the higher the flow rate needs to be to limit temperature loss of the fluid.
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31.
  • Jensen, Emil, et al. (författare)
  • Changes in temperature in preheated crystalloids at ambient temperatures relevant to a prehospital setting: an experimental simulation study with the application of prehospital treatment of trauma patients suffering from accidental hypothermia
  • 2024
  • Ingår i: BMC EMERGENCY MEDICINE. - : BioMed Central (BMC). - 1471-227X. ; 24:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Background Accidental hypothermia is common in all trauma patients and contributes to the lethal diamond, increasing both morbidity and mortality. In hypotensive shock, fluid resuscitation is recommended using fluids with a temperature of 37-42 degrees, as fluid temperature can decrease the patient's body temperature. In Sweden, virtually all prehospital services use preheated fluids. The aim of the present study was to investigate how the temperature of preheated infusion fluids is affected by the ambient temperatures and flow rates relevant for prehospital emergency care.Methods In this experimental simulation study, temperature changes in crystalloids preheated to 39 degrees C were evaluated. The fluid temperature changes were measured both in the infusion bag and at the patient end of the infusion system. Measurements were conducted in conditions relevant to prehospital emergency care, with ambient temperatures varying between - 4 and 28 degrees C and flow rates of 1000 ml/h and 6000 ml/h, through an uninsulated infusion set at a length of 175 cm.Results The flow rate and ambient temperature affected the temperature in the infusion fluid both in the infusion bag and at the patient end of the system. A lower ambient temperature and lower flow rate were both associated with a greater temperature loss in the infusion fluid.Conclusion This study shows that both a high infusion rate and a high ambient temperature are needed if an infusion fluid preheated to 39 degrees C is to remain above 37 degrees C when it reaches the patient using a 175-cm-long uninsulated infusion set. It is apparent that the lower the ambient temperature, the higher the flow rate needs to be to limit temperature loss of the fluid.
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32.
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33.
  • Joensuu, Heikki, et al. (författare)
  • Effect of Adjuvant Trastuzumab for a Duration of 9 Weeks vs 1 Year With Concomitant Chemotherapy for Early Human Epidermal Growth Factor Receptor 2-Positive Breast Cancer The SOLD Randomized Clinical Trial
  • 2018
  • Ingår i: JAMA Oncology. - : AMER MEDICAL ASSOC. - 2374-2437 .- 2374-2445. ; 4:9, s. 1199-1206
  • Tidskriftsartikel (refereegranskat)abstract
    • Importance: Trastuzumab plus chemotherapy is the standard adjuvant treatment for patients with human epidermal growth factor receptor 2 (HER2)-positive early breast cancer. While the standard duration of trastuzumab treatment is 12 months, the benefits and harms of trastuzumab continued beyond the chemotherapy are unclear.Objective: To evaluate the efficacy and safety of adjuvant trastuzumab continued beyond chemotherapy in women treated with up-front chemotherapy containing a taxane and trastuzumab.Design, Setting, and Participants: Open-label, randomized (1:1) clinical trial including women with HER2-positive breast cancer. Chemotherapy was identical in the 2 groups, consisting of 3 cycles of 3-weekly docetaxel (either 80 or 100 mg/m2) plus trastuzumab for 9 weeks, followed by 3 cycles of fluorouracil, epirubicin, and cyclophosphamide. Thereafter, no trastuzumab was administered in the 9-week group, whereas controls received trastuzumab to complete 1 year of administration. Disease-free survival (DFS) was compared between the groups using a Cox model and the noninferiority approach. The estimated sample size was 2168 patients (1-sided testing, with a relative noninferiority margin of 1.3). From January 3, 2008, to December 16, 2014, 2176 patients were accrued from 7 countries.Intervention: Docetaxel plus trastuzumab for 9 weeks, followed by 3 cycles of fluorouracil, epirubicin, and cyclophosphamide in both groups. Controls continued trastuzumab to 1 year.Main Outcomes and Measures: The primary objective was DFS; secondary objectives included distant disease–free survival, overall survival, cardiac DFS, and safety.Results: In the 2174 women analyzed, median age was 56 (interquartile range [IQR], 48-64) years. The median follow-up was 5.2 (IQR, 3.8-6.7) years. Noninferiority of the 9-week treatment could not be demonstrated for DFS (hazard ratio, 1.39; 2-sided 90% CI, 1.12-1.72). Distant disease–free survival and overall survival did not differ substantially between the groups. Thirty-six (3%) and 21 (2%) patients in the 1-year and the 9-week groups, respectively, had cardiac failure; the left ventricle ejection fraction was better maintained in the 9-week group. An interaction was detected between the docetaxel dose and DFS; patients in the 9-week group treated with 80 mg/m2 had inferior and those treated with 100 mg/m2 had similar DFS as patients in the 1-year group.Conclusions and Relevance: Nine weeks of trastuzumab was not noninferior to 1 year of trastuzumab when given with similar chemotherapy. Cardiac safety was better in the 9-week group. The docetaxel dosing with trastuzumab requires further study.Trial Registration: ClinicalTrials.gov Identifier: NCT00593697
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34.
  • Johansson, Helena, et al. (författare)
  • Reasons for bias in ambulance clinicians’ assessments of non-conveyed patients : a mixed-methods study
  • 2022
  • Ingår i: BMC Emergency Medicine. - : Springer Nature. - 1471-227X. ; 22:1
  • Tidskriftsartikel (refereegranskat)abstract
    • The number of ambulance assignments and the influx of patients to the emergency departments (EDs) in Sweden have increased in recent years. This is one reason the protocol for prehospital emergency care was developed around referring patients for non-conveyance, either through the see-and-convey elsewhere approach or through the see-and-treat approach. However, this protocol has led to challenges in patient assessments.
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35.
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36.
  • Johansson, Helena, et al. (författare)
  • Tissue factor produced by the endocrine cells of the islets of Langerhans is associated with a negative outcome of clinical islet transplantation
  • 2005
  • Ingår i: Diabetes. - : American Diabetes Association. - 0012-1797 .- 1939-327X. ; 54:6, s. 1755-62
  • Tidskriftsartikel (refereegranskat)abstract
    • There are strong indications that only a small fraction of grafts successfully engraft in clinical islet transplantation. One explanation may be the instant blood-mediated inflammatory reaction (IBMIR) elicited by tissue factor, which is produced by the endocrine cells. In the present study, we show that islets intended for islet transplantation produce tissue factor in both the transmembrane and the alternatively spliced form and that the membrane-bound form is released as microparticles often associated with both insulin and glucagon granules. A low-molecular mass factor VIIa (FVIIa) inhibitor that indirectly blocks both forms of tissue factor was shown in vitro to be a promising drug to eliminate the IBMIR. Thrombin-antithrombin complex (TAT) and FVIIa-antithrombin complex (FVIIa-AT) were measured in nine patients who together received 20 infusions of isolated human islets. Both the TAT and FVIIa-AT complexes increased rapidly within 15-60 min after infusion. When the initial TAT and FVIIa-AT levels were plotted against the increase in C-peptide concentration after 7 days, patients with an initially strong IBMIR showed no significant increase in insulin synthesis after 7 days. In conclusion, tissue factor present in both the islets and the culture medium and elicits IBMIR, which affects the function of the transplanted islets.
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37.
  • Johnson, Randi K., et al. (författare)
  • Metabolite-related dietary patterns and the development of islet autoimmunity
  • 2019
  • Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 9:1
  • Tidskriftsartikel (refereegranskat)abstract
    • The role of diet in type 1 diabetes development is poorly understood. Metabolites, which reflect dietary response, may help elucidate this role. We explored metabolomics and lipidomics differences between 352 cases of islet autoimmunity (IA) and controls in the TEDDY (The Environmental Determinants of Diabetes in the Young) study. We created dietary patterns reflecting pre-IA metabolite differences between groups and examined their association with IA. Secondary outcomes included IA cases positive for multiple autoantibodies (mAb+). The association of 853 plasma metabolites with outcomes was tested at seroconversion to IA, just prior to seroconversion, and during infancy. Key compounds in enriched metabolite sets were used to create dietary patterns reflecting metabolite composition, which were then tested for association with outcomes in the nested case-control subset and the full TEDDY cohort. Unsaturated phosphatidylcholines, sphingomyelins, phosphatidylethanolamines, glucosylceramides, and phospholipid ethers in infancy were inversely associated with mAb+ risk, while dicarboxylic acids were associated with an increased risk. An infancy dietary pattern representing higher levels of unsaturated phosphatidylcholines and phospholipid ethers, and lower sphingomyelins was protective for mAb+ in the nested case-control study only. Characterization of this high-risk infant metabolomics profile may help shape the future of early diagnosis or prevention efforts. © 2019, The Author(s).
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38.
  • Jonsdottir, Berglind, et al. (författare)
  • Are Perinatal Events Risk Factors for Childhood Thyroid Autoimmunity?
  • 2017
  • Ingår i: European Thyroid Journal. - : Bioscientifica. - 2235-0640 .- 2235-0802. ; 6:6, s. 298-306
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Environmental and genetic factors possibly trigger thyroid autoimmunity. Studies on perinatal risk factors for childhood thyroid autoimmunity are sparse.Objectives: The aim was to investigate if perinatal factors, family history of autoimmune diseases, and HLA-DQ genotypes contribute to thyroid autoimmunity in the Diabetes Prediction in Skåne (DiPiS) study.Methods: Samples from 1,874 ten-year-old children were analyzed for autoantibodies to thyroid peroxidase (TPOAb), thyroglobulin (TGAb), and HLA-DQ genotypes. Information on perinatal events and family history of autoimmunity was gathered prospectively in questionnaires.Results: Thyroid autoimmunity was found in 6.9% of the children (TPOAb 4.4%, TGAb 5.8%, both autoantibodies 3.3%) and was overrepresented in girls. Prematurity was positively related to TGAb (OR: 2.4, p = 0.003, p c = 0.021). Autoimmune diseases in the family increased the risk of thyroid autoimmunity: TPOAb (OR: 2.2, p = 0.012), any autoantibody (OR: 1.7, p = 0.04), and both autoantibodies (OR: 2.2, p = 0.024). A first-degree relative (FDR) with thyroid disease increased the risk for TPOAb (OR: 2.4, p = 0.03) and both autoantibodies (OR: 2.6, p = 0.03), a FDR or sibling with celiac disease increased the risk for both autoantibodies (OR: 3.7, p = 0.03, and OR: 4.8, p = 0.003), a FDR or sibling with diabetes increased the risk for thyroid autoantibody (OR: 3.0, p = 0.01, and OR: 5.4, p = 0.032), and a father with rheumatic disease increased the risk for TPOAb (OR: 15.2, p = 0.017), TGAb (OR: 11.3, p = 0.029), any autoantibody (OR: 9.6, p = 0.038), and both autoantibodies (OR: 20, p = 0.01).Conclusions: Thyroid autoimmunity was found in 6.9% of the 10-year-old children who were being followed for their risk of type 1 diabetes. No relation to perinatal factors was found, with the exception of a possible association between prematurity and TGAb. Family history of autoimmune diseases increased the risk of thyroid autoimmunity.
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39.
  • Jonsdottir, Berglind, et al. (författare)
  • Childhood thyroid autoimmunity and relation to islet autoantibodies in children at risk for type 1 diabetes in the diabetes prediction in skåne (DiPiS) study
  • 2018
  • Ingår i: Autoimmunity. - : Informa UK Limited. - 0891-6934 .- 1607-842X. ; 51:5, s. 228-237
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: The aim was to determine prevalence and age at seroconversion of thyroid autoimmunity in relation to islet autoantibodies, gender and HLA-DQ genotypes in children with increased risk for type 1 diabetes followed from birth. Methods: In 10-year-old children (n = 1874), blood samples were analysed for autoantibodies against thyroid peroxidase (TPOAb), thyroglobulin (TGAb), glutamic acid decarboxylase 65 (GADA), Zink transporter 8 (ZnT8R/W/QA), insulinoma-associated protein-2 (IA-2A), insulin (IAA) and HLA-DQ genotypes. Prospectively collected samples from 2 years of age were next analysed for TPOAb, and TGAb and, finally, in confirming samples at 11–16 years of age along with TSH and FT4. Frequencies were tested with Chi-square or Fischer’s exact tests, autoantibody levels with Wilcoxon and correlations between autoantibody levels with Spearman’s rank correlation test. Results: The prevalence of thyroid autoimmunity was 6.9%, overrepresented in girls (p <.001) also having higher TPOAb levels at 10 years (p =.049). TPOAb was associated with GADA (p =.002), ZnT8R/W/QA (p =.001) and IA-2A (p =.001) while TGAb were associated with ZnT8R/W/QA (p =.021). In boys only, TPOAb were associated with GADA (p =.002), IA-2A (p =.001), ZnT8R/W/QA (p =.001) and IAA (p =.009), and TGAb with GADA (p =.013), IA-2A (p =.005) and ZnT8R/W/QA (p =.003). Levels of IA-2A correlated to both TPOAb (p =.021) and to TGAb (p =.011). In boys only, levels of GADA and TGAb correlated (p =.009 as did levels of IA-2A and TPOAb (p =.013). The frequency and levels of thyroid autoantibodies increased with age. At follow-up, 22.3% had abnormal thyroid function or were treated with thyroxine. Conclusions: Thyroid autoimmunity and high TPOAb levels were more common in girls. In contrast, in boys only, there was a strong association with as well as correlation between levels of thyroid and islet autoantibodies. It is concluded that while girls may develop autoimmune thyroid disease (AITD) independent of islet autoantibodies, the risk for thyroid disease in boys may be linked to concomitant islet autoimmunity.
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40.
  • Jonsdottir, Berglind, et al. (författare)
  • Early appearance of thyroid autoimmunity in children followed from birth for type 1 diabetes risk
  • Ingår i: The Journal of clinical endocrinology and metabolism. - 1945-7197.
  • Tidskriftsartikel (refereegranskat)abstract
    • PURPOSE: Autoantibodies to thyroid peroxidase (TPOAb) and thyroglobulin (TgAb) define pre-clinical autoimmune thyroid disease (AITD) which can progress to either clinical hypo- or hyperthyroidism. We determined the age at seroconversion in children genetically at risk for type 1 diabetes.METHODS: TPOAb and TgAb seropositivity were determined in 5066 healthy children with HLA DR3 or DR4 containing haplogenotypes from The Environmental Determinants of Diabetes in the Young (TEDDY) Study. Children seropositive on the cross-sectional initial screen at 8-13 years of age had longitudinally collected samples (from 3.5 months of age) screened retrospectively and prospectively for thyroid autoantibodies to identify the age at seroconversion. First-appearing autoantibody was related to sex, HLA genotype, family history of AITD, and subsequent thyroid dysfunction and disease.RESULTS: The youngest appearance of TPOAb and TgAb was 10 and 15 months of age, respectively. Girls had higher incidence rates of both autoantibodies. Family history of AITD was associated with a higher risk of TPOAb hazard ratio [HR] 1.90, 95% confidence interval [CI] 1.17, 3.08; and TgAb HR 2.55, 95% CI 1.91, 3.41. The risk of progressing to hypo- or hyperthyroidism was not different between TgAb and TPOAb, but children with both autoantibodies appearing at the same visit had a higher risk compared to TPOAb appearing first (HR 6.34, 95% CI 2.72, 14.76).MAIN CONCLUSION: Thyroid autoantibodies may appear during the first years of life, especially in girls, and in children with a family history of AITD. Simultaneous appearance of both autoantibodies increases the risk for hypo- or hyperthyroidism.
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41.
  • Krischer, Jeffrey P, et al. (författare)
  • Predicting Islet Cell Autoimmunity and Type 1 Diabetes : An 8-Year TEDDY Study Progress Report
  • 2019
  • Ingår i: Diabetes Care. - : American Diabetes Association. - 1935-5548 .- 0149-5992. ; 42:6, s. 1051-1060
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVE: Assessment of the predictive power of The Environmental Determinants of Diabetes in the Young (TEDDY)-identified risk factors for islet autoimmunity (IA), the type of autoantibody appearing first, and type 1 diabetes (T1D).RESEARCH DESIGN AND METHODS: A total of 7,777 children were followed from birth to a median of 9.1 years of age for the development of islet autoantibodies and progression to T1D. Time-dependent sensitivity, specificity, and receiver operating characteristic (ROC) curves were calculated to provide estimates of their individual and collective ability to predict IA and T1D.RESULTS: HLA genotype (DR3/4 vs. others) was the best predictor for IA (Youden's index J = 0.117) and single nucleotide polymorphism rs2476601, in PTPN22, was the best predictor for insulin autoantibodies (IAA) appearing first (IAA-first) (J = 0.123). For GAD autoantibodies (GADA)-first, weight at 1 year was the best predictor (J = 0.114). In a multivariate model, the area under the ROC curve (AUC) was 0.678 (95% CI 0.655, 0.701), 0.707 (95% CI 0.676, 0.739), and 0.686 (95% CI 0.651, 0.722) for IA, IAA-first, and GADA-first, respectively, at 6 years. The AUC of the prediction model for T1D at 3 years after the appearance of multiple autoantibodies reached 0.706 (95% CI 0.649, 0.762).CONCLUSIONS: Prediction modeling statistics are valuable tools, when applied in a time-until-event setting, to evaluate the ability of risk factors to discriminate between those who will and those who will not get disease. Although significantly associated with IA and T1D, the TEDDY risk factors individually contribute little to prediction. However, in combination, these factors increased IA and T1D prediction substantially.
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42.
  • KTHA #1
  • 2010
  • Samlingsverk (redaktörskap) (populärvet., debatt m.m.)abstract
    • Innehåll|Contents"Gunnar Henriksson: Mannen bakom allt", Ola Andersson, Hans Loord"Nittonhundraåttiofem" Ola Andersson"Landscape as a Body (To Dress)", Katja Grillner"Nya Slussen", Daniel Johansson, Johanna Håkansdotter- Karlsson, Tor Lindstrand, Martin Losos, Victor Mickelsson, Sara Vall, Ann-Charlotte Wiklander, Frida Öhlin"Patchwork: Albano Sustainable Campus", Stephan Bartel, Johan Colding, Hanna Erixon, Henrik Ernstson, Sara Grahn, Matts Ingman, Carl Kärsten, Lars Marcus, Jonas Torsvall"Multireligiös begravningsplats på Järva friområde", Henrik Vogt"Bridging the Gap", Alexis Pontvik"Tullinge Idea Store: Plats, struktur, program" Jesús Azpeitia"Treasures from the Archive: Der Städtebau nach seinen künstlerischen Grundsätzen, Camillo Sitte", Anders Bergström"Reading Architecture and Beauty: Conversations with Architects about a Troubled Relationship, Yael Reisner with Fleur Watson", Frida Rosenberg"Leon Battista Alberti, Identical Copies, and the Early Modern Invention of Architectural Design", Mario Carpo"Three Concepts of Performative Design: Proturbance, Porosity, Venation", Marcelyn Gow, Ulrika Karlsson, Daniel Norell  
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43.
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44.
  • Larsson, Cornelia, et al. (författare)
  • Acceptance and Commitment Therapy for inpatients with psychosis -an acceptability and feasibility single case AB designed study
  • 2022
  • Ingår i: Journal of Contextual Behavioral Science. - : Elsevier. - 2212-1447. ; 25, s. 44-60
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: There is a lack of research on psychological treatments for psychosis in the inpatient setting. Acceptance and Commitment Therapy for psychosis (ACTp) is a diagnose specific adaptation of the transdiagnostic ACT treatment model which has shown promising results in patients with psychosis. Aim: The aim was to explore treatment effects of ACTp on inpatients with psychosis on symptoms, level of functioning, level of activity, psychological flexibility, -health-related quality of life, valued living, and to explore the acceptability and feasibility of ACTp. Method: Twelve inpatients with psychosis were treated with 3-10 daily sessions of ACTp in a non-concurrent single case AB design with additional pre-post and mid-measures. The mean age at clinic A was 48.88 (SD = 11.59) and 48.75 (SD = 16.07) at clinic B. We calculated non - overlap of all pairs (NAP) in daily measures, and reliable change index (RCI), and clinical significance in pre-post measures. Results: Half of the participants improved significantly on health-related quality of life and depression in daily measures and on depression and anxiety in pre-post measures. ACTp was quite acceptable and recruitment and the deliverance of therapy in the inpatient setting was feasible. Conclusion: In the present study, participants found the ACTp treatment to be comprehensive and helpful. Recruitment and treatment of inpatients were feasible, however, since most participants were discharged before ACTp protocol was completed, fewer sessions or having sessions more frequently needs further investigation. Daily measurement showed a significant improvement in health-related quality of life and depression for a majority of the participants.
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45.
  • Larsson, Cornelia, et al. (författare)
  • Facial affect recognition in first-episode psychosis is impaired but not associated with psychotic symptoms.
  • 2022
  • Ingår i: Heliyon. - : Elsevier. - 2405-8440. ; 8:9
  • Tidskriftsartikel (refereegranskat)abstract
    • Introduction: Social dysfunction is a key feature of psychotic disorders such as schizophrenia linked to disability. Less is known about social functioning in the early stages of the disorder and if there is an association to psychotic symptoms.Aims: Investigate if antipsychotic drug-naïve or briefly medicated individuals with first-episode psychosis (FEP), have impaired facial affect recognition (FAR) compared to control participants and if psychotic symptoms are associated with the FAR ability.Method: Individuals with FEP (n = 67) and control participants (n = 51) performed a computer-aided FAR task on basic emotions. Psychotic symptoms were assessed with the Positive and Negative Syndrome Scale (PANSS). Group performances were compared using age and gender as covariates. The associations between FAR and performance on the subscales of PANSS were analyzed.Results: Compared to control participants, individuals with FEP were impaired in general FAR (Beta = -2.04 [95 % conf: -3.75/-1.62], p < 0.001) and FAR of negative emotions (Beta = -1.74 [95 % conf: -3.08/-1.22], p < 0.001), driven by difficulties in recognition of anger and disgust. In both groups, there was a pattern of mistaking negative emotions for other negative emotions. There were no significant group differences in FAR of happiness. No significant associations between FAR and psychotic symptoms were observed.Discussion: The results indicate that FAR, an underlying mechanism of social functioning is impaired early in the course of psychotic disorders. Current findings do not support the hypothesis that misinterpretation of facial expressions in individuals with FEP underlies or contributes to symptoms of psychosis.
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46.
  • Lernmark, Åke, et al. (författare)
  • Immunology of β-Cell Destruction
  • 2015. - 2nd
  • Ingår i: Islets of Langerhans. - 9789400766853 ; , s. 1047-1080
  • Bokkapitel (övrigt vetenskapligt/konstnärligt)
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47.
  • Lind, Alexander, et al. (författare)
  • Childhood screening for type 1 diabetes comparing automated multiplex Antibody Detection by Agglutination-PCR (ADAP) with single plex islet autoantibody radiobinding assays
  • 2024
  • Ingår i: EBioMedicine. - : Elsevier. - 2352-3964. ; 104
  • Tidskriftsartikel (refereegranskat)abstract
    • BackgroundTwo or more autoantibodies against either insulin (IAA), glutamic acid decarboxylase (GADA), islet antigen-2 (IA-2A) or zinc transporter 8 (ZnT8A) denote stage 1 (normoglycemia) or stage 2 (dysglycemia) type 1 diabetes prior to stage 3 type 1 diabetes. Automated multiplex Antibody Detection by Agglutination-PCR (ADAP) assays in two laboratories were compared to single plex radiobinding assays (RBA) to define threshold levels for diagnostic specificity and sensitivity.MethodsIAA, GADA, IA-2A and ZnT8A were analysed in 1504 (54% females) population based controls (PBC), 456 (55% females) doctor's office controls (DOC) and 535 (41% females) blood donor controls (BDC) as well as in 2300 (48% females) patients newly diagnosed (1–10 years of age) with stage 3 type 1 diabetes. The thresholds for autoantibody positivity were computed in 100 10-fold cross-validations to separate patients from controls either by maximizing the χ2-statistics (chisq) or using the 98th percentile of specificity (Spec98). Mean and 95% CI for threshold, sensitivity and specificity are presented.FindingsThe ADAP ROC curves of the four autoantibodies showed comparable AUC in the two ADAP laboratories and were higher than RBA. Detection of two or more autoantibodies using chisq showed 0.97 (0.95, 0.99) sensitivity and 0.94 (0.91, 0.97) specificity in ADAP compared to 0.90 (0.88, 0.95) sensitivity and 0.97 (0.94, 0.98) specificity in RBA. Using Spec98, ADAP showed 0.92 (0.89, 0.95) sensitivity and 0.99 (0.98, 1.00) specificity compared to 0.89 (0.77, 0.86) sensitivity and 1.00 (0.99, 1.00) specificity in the RBA. The diagnostic sensitivity and specificity were higher in PBC compared to DOC and BDC.InterpretationADAP was comparable in two laboratories, both comparable to or better than RBA, to define threshold levels for two or more autoantibodies to stage type 1 diabetes.
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48.
  • Lind, Alexander, et al. (författare)
  • Multiplex agglutination-PCR (ADAP) autoantibody assays compared to radiobinding autoantibodies in type 1 diabetes and celiac disease
  • 2022
  • Ingår i: Journal of Immunological Methods. - : Elsevier BV. - 1872-7905 .- 0022-1759. ; 506
  • Tidskriftsartikel (refereegranskat)abstract
    • Multiplex Antibody-Detection by Agglutination-PCR (ADAP) assay was compared to singleplex standard radiobinding assays (RBA) to detect autoantibodies against insulin (IAA), GAD65 (GADA), islet antigen-2 (IA-2A), ZnT8 (ZnT8A) and tissue transglutaminase (TGA). Serum samples from 272 (114F/158M), 15-73 years of age healthy controls and 227 (109F/118M) newly diagnosed type 1 diabetes children, 1-11 years of age, were analyzed in both assay systems.The original WHO standard 97/550 and in-house reference standards for RBA were compared to ADAP. The ADAP and RBA generated parallel reference standards in all assays except TGA. Lower detection limits were observed in the ADAP assay for GADA,IAA and ZnT8A, markedly for TGA, but not for IA-2A. The Receiver Operating Characteristics (ROC) curve AUC analyses for pairwise comparison of ADAP with RBA showed no difference for GADA (n.s.), ADAP greater AUC for IAA (p = 0.005), RBA greater AUC for IA-2A (p = 0.0004) and ZnT8A (p < 0.0001) while ADAP TGA had a greater AUC compared to both RBA TGA-IgG (p < 0.0001) and TGA-IgA (p < 0.0001) . These data suggest that the ADAP and RBA assays are comparable with equal performance for GADA, better ADAP performance for IAA while the RBA showed better performance in both IA-2A and ZnT8A associated with greater heterogeneity in autoantibody levels. The simultaneous analysis of 5 different autoantibodies by ADAP in sample volume reduced to only 4 μL and at an increased lower detection limit in all assays except IA-2A makes the ADAP automated autoantibody assay a distinct advantage for high throughput screening.
  •  
49.
  • Lindgren, Helena, 1965, et al. (författare)
  • Taking the matter into one’s own hands –Women’s experiences of unassited homebirths in Sweden
  • 2017
  • Ingår i: Sexual & Reproductive HealthCare. - : Elsevier BV. - 1877-5756 .- 1877-5764. ; 11, s. 31-35
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: There are no national guidelines or financial support for planned homebirths in Sweden. Some women choose to give birth at home without the assistance of a midwife. The objective of this study was to describe eight women’s experience of unassisted planned homebirth in Sweden. Design: Women who had the experience of an unassisted planned home birth were interviewed. The material was analysed using a phenomenological approach. Results: The essential meaning of the phenomenon giving birth at home without the assistance of a midwife is understood as a conflict between, on one hand, inner responsibility, power and control and on the other hand insecurity in relation to the outside, to other people and to the social system. A wish to be cared for by a midwife is in conflict with the fear of not maintaining integrity and respect in this precious moment of birth. Conclusion: Some women may be more sensitive to attitudes and activities that are routinely performed during pregnancy and childbirth and therefore choose not to turn to any representatives of the medical system. The challenge should be to provide safe care to allwomen so that assistance from a midwife becomes a reality in all settings.
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50.
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